Successful Treatment of Peritoneal Dialysis Related Peritonitis from Multi-Drug Resistant Sphingomonas paucimobilis with Combination Therapy: A Case Report ()
1. Introduction
Sphingomonas paucimobilis is an aerobic, non-spore-forming gram-negative bacillus with a single polar flagellum and slow motility. Initially classified as Pseudomonas paucimobilis in 1977, it was subsequently reclassified as Sphingomonas on the basis of phylogenetic data [1] [2].
Sphingomonas paucimobilis is widely distributed in water and soil and rarely reported in clinical setting [3]. It is thought to be an opportunistic pathogen and has been associated to bacteremia and septicemia caused by contaminated solutions, e.g. distilled water, dialysis solutions, other than infected ulcers in the lower limbs, urinary tract infection, brain and splenic abscesses.
To the best of our knowledge, there are few data regarding Sphingomonas paucimobilis infections in Peritoneal Dialysis (PD) patients, making difficult the treatment of peritonitis caused by this pathogen.
We report a case of successful treatment of Sphingomonas paucimobilis PD related peritonitis.
2. Case Report
A 52-years-old male PD patient presented to our outpatient clinic for a 1-day history of fever and cloudy peritoneal dialysate drainage. He had end stage renal disease due to diabetic nephropathy and had been receiving CCPD scheme for four months (three glucose-bags for a total amount of thirteen litres at night and 1.5-litres bag daily of icodextrin) and no previous history of peritonitis.
On physical examination, his abdomen was painful, with no vomiting or intestinal occlusion signs, and temperature was 38˚C. His peritoneal catheter and the exit site were normal. Laboratory blood tests showed leukocytes 13,410/mm3 (90.7% Neutrophils), C-Reactive Protein (CRP) 6.3 mg/dL and Procalcitonin 0.77 ng/mL (see Table 1). Peritoneal fluid analysis revealed numerous white blood cells (4370 mmc), mainly neutrophils (80%). The peritoneal effluent was tested for bacterial culture in “BACTEC” (Figure 1). The patient was not admitted to our hospital and we started on empiric therapy for peritonitis with 250 mg of piperacillin-tazobactam per liter of dialyser solution and 20 mg of teicoplanin per liter of dialyser solution, both intraperitoneally. The peritoneal effluent bacterial culture was positive after four days of incubation, and the subcultures, once inoculated to solid media, became positive for a gram negative, non-fermenting, and catalase- and oxidase-positive bacteria. The bacterium detected was Sphingomonas paucimobilis. The susceptibility testing showed antibiotic sensitivity to cefepime, ceftazidime, levofloxacin and meropenem and resistance to amikacina and imipenem.
After three days from the beginning of the empiric antibiotic therapy, the patient presented an improvement in the clinical symptoms, with the disappearance of abdominal pain, resolution of fever and neutrophilic leukocytosis. Leukocytes were still present in the dialysate drainage (even at the fifth day of observation), with CRP and procalcitonin levels persistently high and a decrease in peritoneal ultrafiltrate (see Table 1).
According to the susceptibility testing, we discontinued piperacillin-tazobactam and teicoplanin and started an intraperitoneal therapy with meropenem (250 mg/L) and ciproxin (100 mg/L), and the patient continued performing his usual CCPD scheme.
After three days of treatment, the microscopic analysis of the peritoneal fluid showed less of five 15 leucocytes/mmc, without bacterial growth, in association with a significant decrease of serum CRP and normalization of serum procalcitonin (see Table 1). The antibiotic therapy was maintained for up to three weeks. The subsequent analyses showed sterile dialysate drainage on day 7 and on day 14 after the end of the antibiotic treatment with intraperitoneal meropenem and ciprofloxacin. No relapse of peritonitis occurred during 18 months of follow-up.
3. Discussion
This case report shows successful treatment of peritonitis by Sphingomonas paucimobilis by intraperitoneal administration of meropenem and ciprofloxacin in a peritoneal patient on a CCPD scheme, not hospitalized.
Sphingomonas paucimobilis is widely distributed in nature, thus in soil and aquatic environments, such as drinking and distilled water [4]. It has been also found in nosocomial environments, but infrequently in hemodialysis fluids. Nevertheless, it rarely affects humans but it is associated with high antibiotic resistance [5]. Moreover, Sphingomonas are able to form dense biofilms with the risks of relapsing and/or being resistant to catheter-associated infections [6].
Currently, no recommendation is available for antimicrobial therapy against Sphingomonas infections probably because it is an emerging pathogen with an unpredictable antibiotic sensitivity and a high antibiotic resistance. Additionally, PD-related peritonitis caused by this organism is very rare [7].
To our knowledge, there are only 14 cases reporting Sphingomonas paucimobilis associated peritonitis. As shown in Table 2 [8] - [19], clinical outcomes in infected patients were heterogeneous: indeed, a complete resolution of the infection was reported in 8 patients, whereas in the remaining 6 patients, peritoneal catheter was removed and PD was discontinued.
In the case of success of antibiotic therapy, the intravenous route was used in 1 out of 8 cases, whereas the intraperitoneal route was used in 7 cases.
The antibiotic classes used in this infection were heterogeneous, including trimethoprim plus sulfamethoxazole, carbapenems, ciprofloxacin, and aminoglycosides.
Considering the lack of uniformity in the class of antibiotics and route of administration, as well as the antibiogram (aminoglycosides and imipenem resistance), we decided to use a combination of meropenem and ciprofloxacin by intraperitoneal route for a duration of three weeks. This antibiotic schedule allowed us to maintain our patient in CCPD with no need of hospital admission. Furthermore, no relapses were reported after 18 months of follow-up.
As reported in other cases (Table 2), we were not able to identify the source of infection, because the pathogen was isolated neither in the dialysis solution, nor in other solutions used for our patients. Considering that the patient started dialysis after only four months, we cannot exclude that infection was contracted during surgery for peritoneal catheter, though no cases were reported in our hospital [20].
In conclusion, Sphingomonas paucimobilis is a virulent and multi-drug resistant pathogen that may seldom induce a harmful peritonitis in PD patients, leading to treatment failure and catheter removal in the majority of patients [21]. In our case, the intraperitoneal administration of an association of meropenem and ciprofloxacin was able to eradicate peritonitis, with no need of hospitalization, and allowed us to maintain our patient on his CCPD scheme.
No definitive guidelines are available to treat PD-related peritonitis caused by Sphingomonas paucimobilis. Various antimicrobials (single or associations) and routes of administration were described, leading to different outcomes. The high antibiotic resistance and the inadequate dosage of antibiotics (to avoid an impairment of residual renal function) might be responsible for the high rate of
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Table 2. Summary of reported peritoneal dialysis-related peritonitis cases caused by Sphingomonas paucimobilis spp. Legend: IP: intraperitoneally; IV: intravenously; NR: not revealed.
treatment failure with this new-emerging organism. Combination therapy of antimicrobials might be beneficial to overcome antibiotic resistance, but more studies are needed to confirm our success and develop treatment guidelines.